title: Bedside to bench: role of muscarinic receptor activation in ultrarapid growth of colorectal cancer in a patient with pheochromocytoma.
abstract: An elderly man with long-standing, nonresectable pheochromocytoma had rapid development of rectal adenocarcinoma despite close endoscopic surveillance. We determined that the patient's colorectal cancer overexpressed muscarinic receptor subtype 3, whereas his pheochromocytoma expressed choline acetyltransferase, an enzyme required to produce acetylcholine, which is a muscarinic receptor agonist. These findings suggested that acetylcholine release from the pheochromocytoma stimulated rapid growth of the rectal neoplasm. As proof of principle, we found that culture media conditioned by pheochromocytoma cells stimulates proliferation of a human colon cancer cell line, an effect attenuated by atropine, a muscarinic receptor inhibitor. Our observations provide both clinical and laboratory evidence that muscarinic receptor agonists promote the growth of colorectal neoplasia.
authors.affiliation: Division of Gastroenterology & Hepatology, University of Maryland School of Medicine, Baltimore, MD; VA Maryland Health Care System, Baltimore, MD. Electronic address: evonrose@medicine.umaryland.edu.
authors.forename: Erik C
authors.initials: EC
authors.lastname: von Rosenvinge
authors.forename: Kunrong
authors.initials: K
authors.lastname: Cheng
authors.forename: Cinthia B
authors.initials: CB
authors.lastname: Drachenberg
authors.forename: Carol B
authors.initials: CB
authors.lastname: Fowler
authors.forename: David L
authors.initials: DL
authors.lastname: Evers
authors.forename: Guofeng
authors.initials: G
authors.lastname: Xie
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Raufman
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D000368:Aged; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D008297:Male; D010673:Pheochromocytoma / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D011976:Receptors, Muscarinic / Q000378:metabolism / Q000502:physiology*
chemical_list: D011976:Receptors, Muscarinic; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine
keywords: ChAT; M3R; PCR; choline acetyltransferase; muscarinic receptor subtype 3; polymerase chain reaction